Influence of a fibric acid type of hypolipidemic agent on the oxidative metabolism of arachidonic acid by liver microsomal cytochrome P-450

J. Capdevila, Y. R. Kim, C. Martin-Wixtrom, J R Falck, S. Manna, R. W. Estabrook

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Abstract

The regiospecificity of arachidonic acid oxygenation, catalyzed by rat liver microsomal fractions in the presence of NADPH, can be altered by animal pretreatment with a fibric acid type of hypolipidemic drug, ciprofibrate. While microsomal fractions isolated from either control or phenobarbital-treated animals oxygenate arachidonic acid to mainly epoxyeicosatrienoic acids (EETs), animal pretreatment with ciprofibrate results in an eightfold stimulation of ω and ω-1 oxidation, concomitant with a net decrease in the formation of both HETEs and EETs. The isomeric composition of the EETs and of the ω and ω-1 oxidation products formed is also dependent on the type of animal pretreatment. Associated decreases in the amounts of HETEs and the rate of hydrogen peroxide formation suggests a modification of the "uncoupler action" of arachidonic acid during the function of different cytochromes P-450.

Original languageEnglish (US)
Pages (from-to)8-19
Number of pages12
JournalArchives of Biochemistry and Biophysics
Volume243
Issue number1
DOIs
StatePublished - Nov 15 1985

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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